rs78446

Variant names:

• chr22-48783199-A-G
• rs78446
• ENST00000336769.9:c.391-67559A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000336769.9(TAFA5):​c.391-67559A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.395 in 152,088 control chromosomes in the GnomAD database, including 12,144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.39 (12144 hom., cov: 34)
• Consequence: TAFA5 ENST00000336769.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 5 publications found

Genes affected

TAFA5 (HGNC:21592): (TAFA chemokine like family member 5) This gene is a member of the TAFA family which is composed of five highly homologous genes that encode small secreted proteins. These proteins contain conserved cysteine residues at fixed positions, and are distantly related to MIP-1alpha, a member of the CC-chemokine family. The TAFA proteins are predominantly expressed in specific regions of the brain, and are postulated to function as brain-specific chemokines or neurokines that act as regulators of immune and nervous cells. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.422 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAFA5	ENST00000336769.9	c.391-67559A>G		intron_variant	Intron 3 of 3	4		ENSP00000336812.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60033 AN: 151970 Hom.: 12140 Cov.: 34

Gnomad AFR AF: 0.423

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.316

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.400

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.427

Gnomad OTH AF: 0.395

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.395 AC: 60058 AN: 152088 Hom.: 12144 Cov.: 34 AF XY: 0.388 AC XY: 28874 AN XY: 74344

African (AFR) AF: 0.423 AC: 17521 AN: 41438

American (AMR) AF: 0.321 AC: 4908 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1098 AN: 3470

East Asian (EAS) AF: 0.163 AC: 841 AN: 5168

South Asian (SAS) AF: 0.220 AC: 1063 AN: 4830

European-Finnish (FIN) AF: 0.400 AC: 4233 AN: 10582

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.427 AC: 29010 AN: 68002

Other (OTH) AF: 0.389 AC: 821 AN: 2108

Alfa AF: 0.404 Hom.: 21365

Bravo AF: 0.391

Asia WGS AF: 0.206 AC: 716 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.34
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs78446; hg19: chr22-49179011;